What is PAH?
Pulmonary arterial
hypertension (PAH) is a syndrome characterised by a progressive increase in
pulmonary vascular resistance leading to right ventricular overload and
eventually to right ventricular failure and premature death.1
The increase in pulmonary vascular resistance is related to a
number of progressive changes in the pulmonary arterioles, including:
- Vasoconstriction
- obstructive Remodelling of the pulmonary vessel wall through proliferation in the various layers of the blood vessel wall (smooth muscle cell and endothelial cell proliferation)
- in-situ thrombosis.
The main histological features include medial Hypertrophy,
intimal thickening, adventitial thickening, plexiform lesions and in-situ
thrombosis (Figure 1). The plexifom lesion represents a focal proliferation of
endothelial and smooth muscle cells and is pathognomonic of Pulmonary Arterial
Hypertension (PAH).
Pulmonary Arterial Hypertension (PAH) is defined as a sustained
elevation of mean pulmonary arterial pressure to more than 25 mmHg at rest
or to more than 30 mmHg while exercising, with a normal pulmonary wedge
pressure (< 15 mmHg).2
In most cases the earliest symptom is Dyspnoea
on physical exertion. Other symptoms include syncope or near syncope, fatigue
and peripheral oedema.3,4 Chest tightness and pain similar to
angina may occur, particularly on physical exertion.
References
1. Sitbon O et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 2005; 111: 3105-3111
2. Galiè N, Torbicki A, Barst RJ, et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. Eur Heart J 2004;25:2243-2278.
3. Gaine SP, Rubin LJ. Primary Pulmonary Hypertension. Lancet 1998; 352: 719−25.
4. Barst RJ et al. Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43(Suppl S): 40S-47S
1. Sitbon O et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 2005; 111: 3105-3111
2. Galiè N, Torbicki A, Barst RJ, et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. Eur Heart J 2004;25:2243-2278.
3. Gaine SP, Rubin LJ. Primary Pulmonary Hypertension. Lancet 1998; 352: 719−25.
4. Barst RJ et al. Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43(Suppl S): 40S-47S
What is PAH in Systemic Sclerosis (SSc)?
The connection between PAH and Systemic Sclerosis
Pulmonary arterial
hypertension (PAH) occurs in approximately one in seven scleroderma
patients.1 Pulmonary complications, namely PAH and pulmonary
fibrosis, are a common cause of death in SSc patients.2
Unfortunately, with such symptoms as breathlessness, fatigue on exercise and
syncope, it can masquerade as other respiratory or cardiac complaints with
devastating consequences.3, 4 Furthermore, some patients may have
already reduced daily activities (i.e. mobility problems) and breathlessness
may not be the first symptom. Therefore, PAH needs to be considered in the
daily management of SSc patients and screening is the key to establishing early
diagnosis. International guidelines recommend screening by Doppler
echocardiography annually and/or in the presence of unexplained breathlessness.1,
4, 5 Effective treatments are now available which may improve quality of
life and exercise capacity, slow disease progression and improve long-term
outcome.6
If you suspect PAH, consider referring the patient to a centre with expertise in PAH.
If you suspect PAH, consider referring the patient to a centre with expertise in PAH.
References
1. Hachulla E, Coghlan JG. A new era in the management of pulmonary arterial hypertension related to scleroderma: endothelin receptor antagonism. Ann Rheum Dis 2004; 63:1009-14.
2. Steen V et al. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis 2007; 940-944
3. Runo JR, Loyd JE. Primary pulmonary hypertension. Lancet 2003; 361:1533-44.
4. McGoon M, Gutterman D, Steen V et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004; 126:14S−34S.
5.Galie N, Torbicki A, Barst R et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J. 2004; 25:2243-78.
6.Badesch DB, Abman SH, Ahearn GS et al. Medical therapy for pulmonary arterial hypertension. ACCP evidence-based clinical practice guidelines. Chest 2004; 126:35S-62S.
1. Hachulla E, Coghlan JG. A new era in the management of pulmonary arterial hypertension related to scleroderma: endothelin receptor antagonism. Ann Rheum Dis 2004; 63:1009-14.
2. Steen V et al. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis 2007; 940-944
3. Runo JR, Loyd JE. Primary pulmonary hypertension. Lancet 2003; 361:1533-44.
4. McGoon M, Gutterman D, Steen V et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004; 126:14S−34S.
5.Galie N, Torbicki A, Barst R et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J. 2004; 25:2243-78.
6.Badesch DB, Abman SH, Ahearn GS et al. Medical therapy for pulmonary arterial hypertension. ACCP evidence-based clinical practice guidelines. Chest 2004; 126:35S-62S.
What is PAH in Systemic Sclerosis (SSc)?
The connection between PAH and Systemic Sclerosis
Pulmonary arterial
hypertension (PAH) occurs in approximately one in seven scleroderma
patients.1 Pulmonary complications, namely PAH and pulmonary
fibrosis, are a common cause of death in SSc patients.2
Unfortunately, with such symptoms as breathlessness, fatigue on exercise and
syncope, it can masquerade as other respiratory or cardiac complaints with
devastating consequences.3, 4 Furthermore, some patients may have
already reduced daily activities (i.e. mobility problems) and breathlessness
may not be the first symptom. Therefore, PAH needs to be considered in the
daily management of SSc patients and screening is the key to establishing early
diagnosis. International guidelines recommend screening by Doppler
echocardiography annually and/or in the presence of unexplained breathlessness.1,
4, 5 Effective treatments are now available which may improve quality of
life and exercise capacity, slow disease progression and improve long-term
outcome.6
If you suspect PAH, consider referring the patient to a centre with expertise in PAH.
If you suspect PAH, consider referring the patient to a centre with expertise in PAH.
References
1. Hachulla E, Coghlan JG. A new era in the management of pulmonary arterial hypertension related to scleroderma: endothelin receptor antagonism. Ann Rheum Dis 2004; 63:1009-14.
2. Steen V et al. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis 2007; 940-944
3. Runo JR, Loyd JE. Primary pulmonary hypertension. Lancet 2003; 361:1533-44.
4. McGoon M, Gutterman D, Steen V et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004; 126:14S−34S.
5.Galie N, Torbicki A, Barst R et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J. 2004; 25:2243-78.
6.Badesch DB, Abman SH, Ahearn GS et al. Medical therapy for pulmonary arterial hypertension. ACCP evidence-based clinical practice guidelines. Chest 2004; 126:35S-62S.
1. Hachulla E, Coghlan JG. A new era in the management of pulmonary arterial hypertension related to scleroderma: endothelin receptor antagonism. Ann Rheum Dis 2004; 63:1009-14.
2. Steen V et al. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis 2007; 940-944
3. Runo JR, Loyd JE. Primary pulmonary hypertension. Lancet 2003; 361:1533-44.
4. McGoon M, Gutterman D, Steen V et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004; 126:14S−34S.
5.Galie N, Torbicki A, Barst R et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J. 2004; 25:2243-78.
6.Badesch DB, Abman SH, Ahearn GS et al. Medical therapy for pulmonary arterial hypertension. ACCP evidence-based clinical practice guidelines. Chest 2004; 126:35S-62S.
How is PAH diagnosed?
The early symptoms of Pulmonary arterial
hypertension (PAH) -such as Dyspnoea, dizziness and fatigue - are
often mild and are common to many other conditions. At rest there are often no
symptoms and no apparent signs of illness. As a result, diagnosis can be
delayed for months or even years meaning that Pulmonary Arterial Hypertension
(PAH) is frequently not recognised until the disease is relatively advanced.1
Pulmonary Arterial Hypertension (PAH) is often diagnosed only once other
conditions have been investigated and ruled out.
The non-specific nature of symptoms associated with Pulmonary
Arterial Hypertension (PAH) means that the diagnosis cannot be made on symptoms
alone. A series of investigations is required to make an initial diagnosis, to
refine that diagnosis in terms of clinical class of pulmonary hypertension
(please click here
for classification of pulmonary hypertension) and to evaluate the degree of
functional and haemodynamic impairment (Figure 2). Consequently, it can
be useful to adopt a four stage approach:
1.
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Clinical suspicion of
pulmonary hypertension
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2.
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Detection of pulmonary
hypertension
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3.
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Identify other causes of
Pulmonary hypertension
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References
1. Gaine SP, Rubin LJ. Primary Pulmonary Hypertension. Lancet 1998; 352: 719-25- 2. Barst RJ, McGoon M, Torbicki A et al. Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2004;43 (Suppl S): 40S-47S 3. Galiè N, Torbicki A, Barst RJ, et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. Eur Heart J 2004;25:2243-2278. 4. Sitbon O, Humbert M, Jaïs X et al. Long-term response to Calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 2005; 11:3105-11 5. ATS. ATS statement: guidelines for the 6-minute walk test. Am J Crit Care 2002; 166: 111-7. How is PAH treated?
There is currently no cure for Pulmonary arterial
hypertension (PAH) but advances in understanding how the disease develops
(see section: Why does
PAH develop? ) means that there are now
treatments available which have helped to improve prognosis for patients with
this disease.
The main treatment options for patients with Pulmonary Arterial
Hypertension (PAH) are:1
Treatments
that are routinely used but with little evidence of an impact on the disease:
Treatments
that have been specifically studied in Pulmonary Arterial Hypertension (PAH)
In very severe cases surgical options may be considered:
References
1. Humbert H et al. Treatment of pulmonary arterial hypertension. N Engl J Med 2004; 351: 1425-36 2. Sitbon O, Humbert M, Jaïs X et al. Long-term response to Calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 2005; 11:3105-11 3. Channick RN, Simonneau G, Sitbon O et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 2001;358:1119-23 4. ESC Guidelines. Guidelines to diagnosis and treatment of pulmonary arterial hypertension. European Heart Journal 2004; 25:2243-78 5. Galiè N et al. Sildenafil citrate treatment for pulmonary arterial hypertension. N Engl J Med 2005; 353: 2148-57 Assessing the severity of PAH
The severity of symptoms and the degree of physical limitation
in patients with Pulmonary Arterial Hypertension (PAH) may be assessed by World Health Organization
functional class, WHO FC (see Table 1 below). Such assessment provides
useful information on the current level of physical function, correlates to
prognosis and can help guide decisions on therapy. There are four WHO
functional classes for Pulmonary
Arterial Hypertension (PAH), with class I being the least severe and class
IV being the most advanced.1
Pulmonary Arterial Hypertension (PAH) is a devastating disease,
which can progress rapidly, even in mildly symptomatic patients. Without
treatment, patients in WHO FC II can rapidly deteriorate within 6 months to
more advanced Pulmonary Arterial Hypertension (PAH) as evidenced by progression
of symptoms.2
Table 1. NYHA/WHO Classification of Functional Status of
Patients With Pulmonary Hypertension1
References
1. Barst RJ, McGoon M, Torbicki A, et al. Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2004;43:40S-47S. 2. Galiè N, Rubin LJ, Hoeper MM et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet 2008; 371: 2093-2100 Early identification and intervention of PAH
Early diagnosis and therapeutic intervention may offer improved
outlook for patients. Prognosis and response to treatment have both been shown
to be better for patients in less severe WHO functional class
(WHO FC) compared with those who do not begin targeted therapy until their
Pulmonary Arterial Hypertension (PAH) is in a more severe stage (ie, WHO FC
III/IV)1 (see section, ‘Assessing the
severity of PAH' ).
By recognising and treating patients as early as possible,
disease progression may be delayed. However, this poses a challenge to
healthcare professionals because many of the initial symptoms of Pulmonary
Arterial Hypertension (PAH) - breathlessness, chest tightness and fatigue - are
mild and non-specific and so many patients are diagnosed when their disease is
already quite severe.2 Although the mean time from onset to
diagnosis is estimated to be approximately two years,2 different
patients will progress at different rates, which depend on various factors (see
section, ‘How is PAH
diagnosed?' ) . This makes it even more
important to diagnose early.
References
1. Sitbon O, Humbert M, Nunes H, et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol 2002;40:780-788. 2. Humbert M, Sitbon O, Chaouat A, et al. Pulmonary arterial hypertension in France: results from a national registry. Am.J.Respir.Crit Care Med. 2006;173:1023-1030. Screening for PAH
The key to early diagnosis is introducing screening for high
risk patient populations if they are asymptomatic.
High risk patient populations include:
• Family members of a patient with familial Pulmonary Arterial Hypertension (PAH) • Patients with systemic sclerosis (SSc) • Patients with HIV • Patients with portopulmonary hypertension (PoPH)
The results of a disease registry in France indicated that without
screening, the majority of patients were diagnosed in FC III or FC IV, and only
24% of patients were in FC II at diagnosis.1 (See Fig. 1, left
panel.) Furthermore, the results of a national screening programme in a
high-risk population indicated that it is possible to detect Pulmonary Arterial
Hypertension (PAH) in an earlier stage in a high-risk population (see Fig. 1,
right panel).2
Figure
1. WHO FC at diagnosis, with or without screening
Humbert et al 2006 Am.J.Respir.Crit Care Med. 173, Hachulla et al 2005 Arthritis Rheum. 52
International guidelines now recommend annual screening
high-risk groups with Doppler
echocardiography.3-5 Doppler echocardiography is currently the
most effective method for screening, however, for a definitive diagnosis right heart
catheterisation has to be performed (see ‘How is PAH diagnosed?' ).
References
1. Humbert M, Sitbon O, Chaouat A, et al. Pulmonary arterial hypertension in France: results from a national registry. Am.J.Respir.Crit Care Med. 2006;173:1023-1030. 2. Hachulla E, Gressin V, Guillevin L, et al. Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis Rheum. 2005;52:3792-3800. 3. Hachulla E and Coghlan JG. A new era in the management of pulmonary arterial hypertension related to scleroderma: endothelin receptor antagonism. Ann.Rheum.Dis. 2004;63:1009-1014. 4. Galiè N, Torbicki A, Barst RJ, et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension: The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J 2004;25:2243-2278. 5. McGoon M, Gutterman D, Steen V, et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004;126:14S-34S. |
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